Clinical and experimental features of MuSK antibody positive MG in Japan

Abstract

We investigated the presence of antibodies (Abs) against muscle-specific tyrosine kinase (MuSK) in Japanese myasthenia gravis (MG) patients. MuSK Abs were found in 23 (27%) of 85 generalized seronegative MG (SNMG) patients but not in any of the ocular MG patients. MuSK Ab-positive patients were characterized as having female dominance (M:F, 5:18), age range at onset 18 to 72 (median 45) years old, and prominent oculobulbar symptoms (100%) with neck (57%) or respiratory (35%) muscle weakness. Limb muscle weakness was comparatively less severe (52%), thymoma absent. Most patients had good responses to simple plasma exchange and steroid therapy. MuSK IgG from all 18 patients was exclusively the IgG 4 subclass and bound mainly with the MuSK Ig 1-2 domain. Serial studies of 12 individuals showed a close correlation between the variation in MuSK Ab titers and MG clinical severity (P = 0.01 by Kruskal-Wallis). MuSK Ab titers were sharply decreased in patients who had a good response to early steroid therapy or simple plasma exchange, but there was no change, or a rapid increase on exacerbation after thymectomy. Measurement of MuSK Ab titers aids in the diagnosis of MG and the monitoring of clinical courses after treatment.

MuSK-antibody-positive myasthenia gravis in a South Asian population

“…This proportion is higher than that reported for Chinese populations (2.5%-4%, northern latitudes 32°-34°), but comparable to that of the Koreans (26.7%, northern latitude 37°) and lower than that of the Japanese (41%, northern latitude 35°) [9][10][11][12]. In contrast to Caucasian populations, the proportion of MuSK-MG in our study together with that of the East-Asian populations did not show any relationship to latitude.…”

Characterization of CD4 and CD8 T cell responses in MuSK myasthenia gravis

“…To date, immunologic studies in patients with MuSK MG have primarily been limited to 1) demonstrating the pathogenic nature of MuSK serum and purified anti-MuSK immunoglobulins in animal transfer studies and in vitro models [8, 13, 28]; 2) establishing that MuSK MG autoantibodies are primarily IgG4 [11, 29–31]; 3) examination of muscle and the thymus gland following thymectomy [4, 5, 32]; and 4) measuring autoantibodies after treatment with rituximab [16, 17]. …”

Mapping autoantigen epitopes: molecular insights into autoantibody-associated disorders of the nervous system

“…c MuSK contains three immunoglobulin (Ig)-like domains and a Frizzled (Fz)-like domain. Anti-MuSK antibodies bind to the three N-linked Ig-like domains and the Fz-like domain [83–85]. d The neuronal P/Q-type voltage-gated calcium channel (VGCC) consists of four repeated domains, each containing six segments (S), with a linker region between S5 and S6.…”